Studies in the Lens and Cataract Biology Section have focussed on the biology of the normal lens and on elucidating mechanisms underlying the process of aging-related cataractogenesis. Dr. Peter Frederikse is studying the role of Alzheimer's Disease biology in cataract. His earlier studies demonstrated the presence of beta-amyloid and other Alzheimer's associated proteins including the presenilins in lens. Studies on a transgenic mouse expressing the human Alzheimer's Precursor Protein have revealed the formation of lens opacities. This finding strengthens the hypothesis that Alzheimer's and cataract, both degenerative diseases of the aging, share some aspects of their underlying molecular biology. Dr. Vasanth Rao and, more recently, Dr. Qui-fang Cheng have investigated the role of the Ras family of small GTPases in the lens. Evidence has been developed that cataracts associated with the cholesterol-lowering agent lovastatin result from impairment of these critical signal transduction molecules because lovastatin blocks production of isoprenoids required for activation of the GTPases. We have targeted the Rho GTPase subfamily for more intensive study, creating a transgenic mouse which is in effect a lens-specific functional knockout of Rho. These mice develop cataracts, sometimes exhibit microphthalmia, ocular hemorrhage and other ocular abnormalities. This should prove to be a powerful model for studying the role of Rho in the lens. Dr. Cheng is working to isolate and characterize a novel group of GTPases which are present in lens fiber cells, but are not detected in lens epithelium or in other tissues. These may be important regulators of differentiation in the lens.